Anticoagulation and sepsis: the opportunity for a new use of heparin?

Sepsis is a leading cause of morbidity and mortality worldwide, and the magnitude of the problem seems higher in developing countries. In the last two decades the accepted standard treatment has resulted in only a slight decrease in mortality, and that decrease has been overshadowed by an almost 300% increase in incidence. Recently has been documented the close relationship between infection, inflammation and coagulation in sepsis has been documented; and although clinically overt disseminated intravascular coagulation may occur in only 30% to 50% of septic patients, the activation of the coagulation cascade is an early and common response to the infectious challenge. Moreover most of the molecules involved in the pro-coagulant state that characterizes sepsis are also powerful generators or amplifiers of the inflammatory response. These findings have fostered a comprehensive body of research regarding biological products with anticoagulant activity, as additional therapies for patients with the most severe states of the sepsis syndrome. This review explains the biological and molecular aspects that support the potential use of anticoagulant treatments in sepsis. Furthermore, we analyze the evidence provided by experimental and pre-clinical studies, which suggest the usefulness of heparin as an effective complementary treatment throughout the clinical stages of the disease.     

An expectation and maximization algorithm for estimating Q?×?E interaction effects

A Markov chain Monte Carlo (MCMC) implemented Bayesian method has been developed to detect quantitative trait loci (QTL) effects and Q × E interaction effects. However, the MCMC algorithm is time consuming due to repeated samplings of QTL parameters. We developed an expectation and maximization (EM) algorithm as an alternative method for detecting QTL and Q × E interaction. Simulation studies and real data analysis showed that the EM algorithm produced comparable result as the Bayesian method, but with a speed many magnitudes faster than the MCMC algorithm. We used the EM algorithm to analyze a well known barley dataset produced by the North American Barley Genome Mapping Project. The dataset contained eight quantitative traits collected from 150 doubled-haploid (DH) lines evaluated in multiple environments. Each line was genotyped for 495 polymorphic markers. The result showed that all eight traits exhibited QTL main effects and Q × E interaction effects. On average, the main effects and Q × E interaction effects contributed 34.56 and 16.23% of the total phenotypic variance, respectively. Furthermore, we found that whether or not a locus shows Q × E interaction does not depend on the presence of main effect.     

When is enough … enough? Effective sampling protocols for estimating the survival rates of seabirds with mark-recapture techniques

Capsule: Lower intensity mark-recapture studies, such as those undertaken by citizen scientists, provide an opportunity to improve the spatial representation of survival estimates for birds. Colonial nesting birds are particularly suited to this because, for many species, large numbers of breeding birds and chicks can be located relatively easily. The minimum level of recapture effort required to accurately estimate true survival rates and detect temporal variation largely depended on the respective ringing effort. Therefore, mark-recapture studies should consider both aspects of the field study when setting or adjusting minimum effort guidelines. Furthermore, achieving reliable estimation with short time-series required more intensive survey designs, highlighting the importance of longevity when planning these studies.

Aims: To provide minimum guidelines of field effort that can be used to manage smaller projects that monitor survival rates, such as those reliant on citizen scientists.

Methods: We conducted a sensitivity analysis that evaluated the statistical power associated with using different mark-recapture survey designs to estimate a fixed ‘true’ survival rate and detect sources of temporal variation and individual heterogeneity within the population.

Results: Isolating temporal variation with a good degree (90%) of certainty required the highest levels of survey effort. Based on the assessed survey designs, we recommend studies that have a ten-year trajectory and a recapture rate of 0.6, aim to mark at least 200 new adults per year. The recommended number of marked individuals will decrease if it is possible to achieve higher rates of recapture. Lower rates of juvenile survival and delayed reproduction mean that seabird mark-recapture survey designs that target both chicks and adults offer only marginal improvements in resolving the survival rates of adults, when compared to designs targeting adults only. However, collecting juvenile mark-recapture data provide access to age-specific vital rates that are also valuable for assessing the population dynamics of seabirds.

Conclusion: The addition of chicks is unlikely to improve the resolution of adult survival rates markedly, although for species with low natal dispersal and earlier ages of maturity, these data may allow the estimation of other vital rates, such as juvenile survival rates and age of maturity. Implementing minimum effort guidelines potentially enables the effective management of smaller mark-recapture studies, thus minimising the risk that studies fail to achieve the data conditions necessary for robust estimation of survival rates.     

Problems with essential fatty acids: time for a new paradigm?

The term ‘essential fatty acid’ is ambiguous and inappropriately inclusive or exclusive of many polyunsaturated fatty acids. When applied most rigidly to linoleate and -linolenate, this term excludes the now well accepted but conditional dietary need for two long chain polyunsaturates (arachidonate and docosahexaenoate) during infancy. In addition, because of the concomitant absence of dietary -linolenate, essential fatty acid deficiency is a seriously flawed model that has probably led to significantly overestimating linoleate requirements. Linoleate and -linolenate are more rapidly β-oxidized and less easily replaced in tissue lipids than the common ‘non-essential’ fatty acids (palmitate, stearate, oleate). Carbon from linoleate and -linolenate is recycled into palmitate and cholesterol in amounts frequently exceeding that used to make long chain polyunsaturates. These observations represent several problems with the concept of ‘essential fatty acid’, a term that connotes a more protected and important fatty acid than those which can be made endogenously. The metabolism of essential and non-essential fatty acids is clearly much more interconnected than previously understood. Replacing the term ‘essential fatty acid’ by existing but less biased terminology, i.e. polyunsaturates, ω3 or ω6 polyunsaturates, or naming the individual fatty acid(s) in question, would improve clarity and would potentially promote broader exploration of the functional and health attributes of polyunsaturated fatty acids.     

Pollen pool heterogeneity in jack pine (Pinus banksiana Lamb.): a problem for estimating outcrossing rates?

Summary Pollen pool heterogeneity, which violates an assumption of the mixed-mating model, is a major potential problem in measuring plant mating systems. In this study, isozyme markers were used to examine pollen pool heterogeneity in two natural populations of jack pine, Pinus banksiana Lamb., in northwestern Ontario, Canada. Population multilocus estimates of outcrossing rate ranged from 0.83 to 0.95 and differed significantly between populations. Single-tree multilocus outcrossing rates were found to be homogeneous among trees in both populations. Computer simulation studies indicated that a consanguineous pollen pool (pollen gametes related to the mother tree) was capable of biasing population outcrossing estimates downward. Random pollen pool heterogeneity (uncorrelated with maternal genotypes) did not appear to affect population outcrossing estimates in the simulations. Heterogeneity G-tests and Spearman rank tests showed that pollen pool heterogeneity existed in the two natural populations examined; however, it did not have a major effect on population outcrossing estimates, since the consanguineous pollen pool detected was probably a relatively minor component of the outcross pollen pool in both populations. In addition, heterogeneity G-tests were found to be not sensitive in detecting pollen pool heterogeneity caused by consanguineous pollen pool.     

Systematics of the Pacific monkey‐faced bats (Chiroptera: Pteropodidae), with a new species of Pteralopex and a new Fijian genus

The fruit‐bat genus Pteralopex comprises the monkey‐faced bats, a group of six endangered species found only in old‐growth forests on certain islands in the south‐west Pacific (the Solomon Islands and Fiji). The taxonomy of the genus is reviewed in detail and updated accordingly. Two ‘cryptic’ biological species are shown to occur in sympatry on both Bougainville and Choiseul in the northern Solomon Islands (corresponding to Pteralopex anceps Andersen, 1909 and a previously undescribed species) and each is accordingly described and reviewed. A new genus (Mirimiri) is erected for the Fijian monkey‐faced bat (formerly Pteralopex acrodonta), which differs greatly both morphologically and genetically from species of Pteralopex in the Solomon Islands. Ecomorphological differences between sympatric Pteralopex species are briefly reviewed, including potential differences in functional morphology and feeding ecology. Geographic patterns of occurrence and future survey priorities for monkey‐faced bats are also discussed.     

Estrogen and mitochondria: a new paradigm for vascular protection?

Mitochondrial dysfunction has been implicated as a cause of age-related disorders, and the mitochondrial theory of aging links aging, exercise, and diet. Endothelial dysfunction is a key paradigm for vascular disease and aging, and there is considerable evidence that exercise and dietary restriction protect against cardiovascular disease. Recent studies demonstrate that estrogen receptors are present in mitochondria and that estrogen promotes mitochondrial efficiency and decreases oxidative stress in the cerebral vasculature. Chronic estrogen treatment increases mitochondrial capacity for oxidative phosphorylation while decreasing production of reactive oxygen species. The effectiveness of estrogen against age-related cardiovascular disorders, including stroke, may thus arise in part from hormonal effects on mitochondrial function. Estrogen-mediated mitochondrial efficiency may also be a contributing factor to the longer lifespan of women.     

What's in a name? Aschersonia insperata: a new pleoanamorphic fungus with characteristics of Aschersonia and Hirsutella

A new anamorphic species from a Philippine tropical forest occurs as reddish-orange to orange, tuberculate stromata on unidentified homopteran larvae, and produces both Aschersonia and Hirsutella-like synanamorphs. A molecular phylogenetic analysis was conducted to determine the most appropriate generic placement for this fungus. Based on its phylogenetic relationships, a comparison of the complexity and persistence of each anamorph, and the speculated relevance of each synanamorph to survival, we describe the new fungus as Aschersonia insperata sp. nov.     

Potential anti-diabetic applications of a new molecule with affinity for β3-Adrenoceptors

β₃-adrenoceptors have been described through both molecular and pharmacological studies. In this context, it has been characterized the β₃-adrenoceptors agonist activity of a new compound (Trecadrine^®), and evaluated whether it exhibits additional activity at β₁ and β₂- adrenoceptor subtypes. In addition, it has been tested its potential anti-diabetic properties in a model of alloxan-induced diabetes in rats. Our data show that Trecadrine^® induces oesophageal muscularis mucosae relaxation, indicating a putative action on β₃-adrenoceptors. In the absence of β₃-adrenoceptors antagonists, assays with β₁ and β₂-adrenergic antagonists reveal a quite remarkable selectivity for β₃-adrenoceptors. Furthermore, it has been suggested that this molecule has hypoglycaemic and lipomobilizing effects, although hypoglycaemia was not related to an increase in insulin secretion in diabetic rats. It is concluded that Trecadrine^® mainly acts through β₃-adrenoceptors, and it may constitute a potential drug in the treatment of diabetes.     

Ion movements and oxygen requirements of asteroids—a theoretical consideration

• 1.1. The total loss of potassium during the stepping cycles executed by the tube feet of starfish has been estimated.
• 2.2. The oxygen requirement necessary to operate an ion pump to replenish this loss has been shown to represent only a small percentage of the total consumption.
• 3.3. The demands of ionic regulation are unlikely to be a limiting factor in animals entering water of reduced salinity.

     

Design of commissioning process for Halcyon™ linac with a new rigid board: A clinical experience

PurposeThis study performed the accurate measurements of beam profiles with a new rigid board, which was consistent with the supplied reference beam profiles (RBPs) for clinical Halcyon model.MethodsPercentage depth doses (PDDs), lateral and diagonal dose profiles were measured and compared with RBPs. A water tank was set on the rigid board bridged Halcyon bore without sagging and source-to-surface distance was 90.0 cm. Field sizes were from 2.0 to 28.0 cm squares and depths of lateral and diagonal dose profiles were 1.3, 5.0, 10.0, and 20.0 cm. For the PDD, the depth of maximum dose (d_max), PDD value at depth of 10.0 cm (PDD₁₀), and absolute dose difference (DD) between RBP and measured beam profiles (MBP) were evaluated. For lateral and diagonal dose profiles, DDs for the whole and divided areas (central, shoulder, and extended areas) defined by third derivative, and distance-to-agreement (DTA) in the penumbra area were evaluated.ResultsFor PDDs, the differences of d_max and PDD₁₀ and DD beyond the d_max were within 1.0 mm, 0.3%, and 1.0%, respectively. For lateral and diagonal dose profiles, the DDs reached approximately 5.0% in the whole area because of penumbra area, while the DDs in the central, shoulder, and extended areas were within 1.0%, 2.0%, and 1.0%, respectively. The DTAs in the penumbra area were within 0.8 mm.ConclusionsThe supplied RBPs can be used clinically owing to the good agreement with the accurate MBPs with rigid board.     

Probiotics for the skin: a new area of potential application?

AIMS: The current study aimed at assessing, in vitro, the potential use of probiotics for the skin. METHODS AND RESULTS: Propionibacteria were chosen as potential probiotics as they are members of the normal cutaneous microbiota. Dairy strains were chosen because of their documented safe use. Production of anti-microbial substances was assessed, against selected skin pathogens. Only production of organic acids was detected. Two of the tested strains were found to exhibit high adhesion to human keratin, in vitro. Despite this high adhesion, no inhibition of skin pathogen adhesion to human keratin was observed. CONCLUSIONS: The current strains assessed may not be optimal for use as skin probiotics. However, the results of the study show that the methodology works for investigating this kind of application. SIGNIFICANCE AND IMPACT OF THE STUDY: Methods for selecting probiotics for potential application on the skin are presented.     

Mouse Fcγ RI: identification and functional characterization of five new alleles

 The mouse Fcgr1 gene encoding the high-affinity IgG receptor (FcγRI) exists as two known alleles, FcγRI-BALB and FcγRI-NOD, and these alleles exhibit functional differences. To determine whether other alleles exist in mouse strains, Fcgr1 coding regions from 35 strains of mice were sequenced and a further five alleles were identified. The FcγRI-BALB and NOD alleles are now designated the "a" and "d" alleles, respectively. Analysis of the five new alleles revealed that although no polymorphisms were observed in the two leader exons, nucleotide and subsequent amino acid changes were observed in the exons encoding the extracellular domains, and transmembrane and cytoplasmic tail. The cDNA of the seven alleles (a–g) were isolated and transiently transfected into COS cells, and IgG-binding studies were performed. Receptors encoded by four of the five new alleles (b, c, f, g) bound IgG2a with high affinity, displaying IgG binding characteristics similar to the a allele (previously FcγRI-BALB). The d allele (previously FcγRI-NOD) and the e allele [derived from Mus spretus (SPRET/Ei)] encoded receptors which showed broader specificity by binding monomeric IgG2a, IgG2b, and IgG3. Received: 26 May 1999 / Revised: 25 October 1999     

Penman-Monteith approaches for estimating crop evapotranspiration in screenhouses—a case study with table-grape

In arid and semi-arid regions many crops are grown under screens or in screenhouses to protect them from excessive radiation, strong winds, hailstorms and insects, and to reduce crop water requirements. Screens modify the crop microclimate, which means that it is necessary to accurately estimate crop water use under screens in order to improve the irrigation management and thereby increase water-use efficiency. The goal of the present study was to develop a set of calibrated relationships between inside and outside climatic variables, which would enable growers to predict crop water use under screens, based on standard external meteorological measurements and evapotranspiration (ET) models. Experiments were carried out in the Jordan Valley region of eastern Israel in a table-grape vineyard that was covered with a transparent screen providing 10 % shading. An eddy covariance system was deployed in the middle of the vineyard and meteorological variables were measured inside and outside the screenhouse. Two ET models were evaluated: a classical Penman-Monteith model (PM) and a Penman-Monteith model modified for screenhouse conditions by the inclusion of an additional boundary-layer resistance (PMsc). Energy-balance closure analysis, presented as a linear relation between half-hourly values of available and consumed energy (1,344 data points), yielded the regression Y?=?1.05X–9.93 (W m^?2), in which Y = sum of latent and sensible heat fluxes, and X = net radiation minus soil heat flux, with R ²?=?0.81. To compensate for overestimation of the eddy fluxes, ET was corrected by forcing the energy balance closure. Average daily ET under the screen was 5.4?±?0.54 mm day^?1, in general agreement with the model estimates and the applied irrigation. The results showed that measured ET under the screen was, on average, 34 % lower than that estimated outside, indicating significant potential water saving through screening irrigated vineyards. The PM model was somewhat more accurate than the PMsc for estimating ET under the screen. A model sensitivity analysis illustrates how changes in certain climatic conditions or screen properties would affect evapotranspiration.     

Molecular substitution rate increases with latitude in butterflies: evidence for a trans‐glacial latitudinal layering of populations?

A well‐documented consequence of repeated global ice ages is the negative relationship between latitude and intraspecific genetic diversity. However, little is known about additional effects of such major climatic events on population genetic structure. Here we studied the phylogeographic structure of five lycaenid butterfly species with varied ecological adaptations, sampled across a latitudinal gradient in the Holarctic region. We found a positive correlation between latitude and substitution rate of mitochondrial DNA sequences in all species investigated. We propose that this result is the signal of increased genetic drift and founder effects during post‐glacial recolonization of northern populations. Given that phylogenetic branch length is the result of a cumulative process over evolutionary time, we hypothesize that a latitudinal layering of populations has generally been maintained during repeated cycles of glaciation, possibly due to a neutral spatial effect and/or local adaptive advantage. This trans‐glacial latitudinal layering could be viewed as a particular case of the more general phenomenon of intraspecific structuring that is created and maintained in a fluctuating environmental gradient.